LONGEVITY MEME NEWSLETTER
July 30 2007
The Longevity Meme Newsletter is a weekly e-mail containing news, opinions and happenings for people interested in healthy life extension: making use of diet, lifestyle choices, technology and proven medical advances to live healthy, longer lives.
- Reports From Transvision 2007
- Fat to Inflammation to Age-Related Disease
- Latest Healthy Life Extension Headlines
REPORTS FROM TRANSVISION 2007
Transvision 2007 was held this past week, a yearly gathering of those interested in furthering transhumanist goals, such as extending the healthy human life span. Presenters included Aubrey de Grey, Ray Kurzweil and other familiar names. Links to a selection of reports from the event can be found in the following post; my focus is healthy life extension, but a wide range of other topics were covered:
"I think Kurzweil's timelines for the next couple of decades are too optimistic, for reasons relating to the incompressibility of human interactions in business cycles. One can of course conceive of technologies (like strong artificial intelligence) that get around that limitation, we being the species that treats limits like red flags, but you have to get them through the process of development first.
"I would be very pleased to see us make the advances needed to achieve indefinite life expectancy - even in the laboratory, in mice - by 2022, but color me skeptical. I think it'll take a couple of decades more unless some very big players decide to jump into rejuvenation research money-first within the next few years."
At least a few groups are presently working hard to convince a range of big players to do just that, from the Methuselah Foundation to the architects of the Longevity Dividend initiative - not to mention the efforts of organizations like the Glenn Foundation to craft a well-funded research environment that attracts more investment to the fight to cure aging.
FAT TO INFLAMMATION TO AGE-RELATED DISEASE
Scientists continue to fill in the gaps remaining in understanding how fat leads to inflammation, which in turn accelerates many of the most common age-related conditions. Being overweight appears to shorten the range on your healthy life span by increasing the rate at which biochemical and cellular damage accumulates:
"In recent years, the immune system has also been implicated in type 2 diabetes - in particular imbalances in cytokines, an immune system component that causes inflammation. ... Macrophages appear in high concentrations in fatty tissue. With funding from the National Institutes of Health, Nadler has traced the mechanism by which the presence of large numbers of fat cells stimulate the macrophages to activate the 12/15-LO gene, and has documented the cascade of inflammatory reactions that results. He has found that the 12/15-LO gene produces two proteins that convert fatty acids into cytokines."
A chain of consequences: more body fat means more macrophages in fatty tissue, which means more cytokines, which means more inflammation. More inflammation brings much greater risk of Alzheimer's, diabetes, heart disease and other more general forms of age-related degeneration. That risk is based upon the greater accumulation of age-related changes in your biochemistry - damage, in other words.
While science will advance to wondrous new heights in the decades to come, it only makes sense to play the odds, take care of the health basics, and increase your chances of living healthily into the era of rejuvenation medicine. We're not there yet, the longevity research community to rival the cancer establishment has yet to be built, and we're all still aging - but most of us are lucky enough to have some modest choice as to how fast degeneration takes us:
The highlights and headlines from the past week follow below.
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Founder, Longevity Meme
LATEST HEALTHY LIFE EXTENSION HEADLINES
To view commentary on the latest news headlines complete with links and references, please visit the daily news section of the Longevity Meme: http://www.longevitymeme.org/news/
Update on State Funding of Stem Cell Research (July 27 2007)
For those keeping track, Forbes notes recent events in the trend towards public funding of stem cell research by US states: "New Jersey voters will decide this November whether to approve borrowing $450 million to pay for stem cell research in the state for 10 years under legislation signed Thursday by Gov. Jon S. Corzine. ... The money would support research on adult and embryonic stem cells. ... The state has already approved spending $270 million to build stem cell research facilities. Several states are competing in stem cell research. California approved spending $3 billion on stem cell research, Connecticut has a $100 million program, Illinois spent $10 million and Maryland awarded $15 million in grants. New Jersey awarded $10 million for research grants earlier this year with money from the state budget." Politicians in other states are also moving forward with similar initiatives; some are larger, such as that put forward by in New York. Distributing public funds for political gain has always been a national pastime, but it seems to be a growth industry of late.
Aging, Gender, Mitochondria, Calorie Restriction (July 27 2007)
A nice confluence of processes in this research: the longevity difference between genders, the role of oxidative damage in aging, how mitochondria cause that oxidative damage, and how calorie restriction changes it all. "Caloric restriction (CR) without malnutrition has been shown to increase maximal life span and delay the rate of aging in a wide range of species. It has been proposed that reduction in energy expenditure and oxidative damage may explain the life-extending effect of CR. Gender also has been shown to influence longevity and energy expenditure in many mammalian species. The aim of the present study was to determine the gender-related differences in rat liver mitochondrial machinery, bioenergetics and oxidative balance in response to short-term CR. ... Female rats showed a higher oxidative capacity and GPx activity than males. This gender dimorphism was not modified by CR. Restricted rats showed slightly increased oxygen consumption, complex III activity and GPx antioxidant activity together with lower levels of oxidative damage. In conclusion, the gender dimorphism in liver mitochondrial oxidative capacity was unaffected by CR, with females showing higher mitochondrial functionality and ROS protection than males."
AC5 and Mouse Longevity (July 26 2007)
Nature reports on a new longevity gene tweak: "Currently, the main focus of ageing research is on using calorie restriction as a way of activating a metabolic 'fountain of youth'. The new discovery, that knocking out a single cardiac gene could lengthen lifespan, was an unexpected byproduct of heart research. ... mutant mice lacking [the gene for protein] AC5 were more resistant to heart failure caused by pressure within the heart. But in the process, the research team also realised that the mutant mice lived longer than their normal counterparts. [Now] they report that the treated mice lived 30% longer and did not develop the heart stress and bone deterioration that often accompanies ageing. ... AC5 could boost longevity by reducing the trauma caused when chemically reactive forms of oxygen accumulate. The accrued damage from these molecules is thought to contribute to ageing. AC5 mutants make more of a protein called ERK2, which regulates oxidative-stress responses. When Vatner and his colleagues increased ERK2 levels in budding yeast, these yeast lived longer. There are several mysteries about the mice lacking AC5. Young mutants weigh the same as their normal counterparts, but elderly AC5 mutants weigh less - even though they eat more. That suggests a metabolic change [which] could be mimicking calorie restriction. It is also possible that mice without AC5 are more resistant to cancer."
More From Transvision 2007 (July 26 2007)
Ronald Bailey brings us another report from Transvision 2007 at Reason Online: "The Tuesday evening session was devoted to another sort of speculative revival technology, cryonics. Presentations were made by three members of the Alcor Life Extension Foundation. ... Alcor currently has 850 members with 78 patients who are cryonically suspended. The first talk was by nanotechnologist Ralph Merkle who gave the standard line that cryonics is an experimental technology for life extension. The question is do you want to be in the experimental group or in the control group? ... Alcor has a team that flies to the bedsides of clients whose hearts are about to stop. Once they do stop, the team begins immediately to try to limit damage to their brains. To do that Alcor technicians pump patients' bodies up with cryoprotectants that prevent the formation of damaging ice crystals. ... Alcor is about to begin experiments with mice to see if they can be cooled and then revived. ... I'm still thinking about that, but it would be far more preferable if Aubrey de Grey and his colleagues succeeded in achieving Longevity Escape Velocity."
Sirtris and SRT501 (July 25 2007)
From the MIT Technology Review, an update on progress at Sirtris Pharmaceuticals. The company continues to push forward with the next compound based on their research into sirtuins and calorie restriction biochemistry: "the drug, SRT501, reduces glucose and improves insulin sensitivity in animal and in vitro studies of the drug's effect on type 2 diabetes. In people, the drug was tested for dose, safety, tolerability, and pharmacokinetics--that is, how well the drug was absorbed, distributed, metabolized, and removed from the body. Phase 1b trials are already under way to test safety and pharmacokinetics on patients with type 2 diabetes. Later-phase trials will test to see if the drug actually works in diabetics. SRT501 is a proprietary chemical developed by Sirtris that's based on the naturally occurring resveratrol that company cofounder David Sinclair of Harvard University has been studying for its effects in extending life span in a number of organisms, including yeast, flies, and mice." The regulatory pipeline is painfully slow and expensive, and forces incrementalism while preventing bold strokes. So we get drugs to gently tweak metabolism to slow aging a little rather than, say, attempts to replace damaged mitochondrial DNA in humans in order to repair an aspect of aging - and those drugs are relegated to patching up a disease rather than attacking the aging process.
Insight Into Alzheimer's Research (July 25 2007)
A long piece at EureAlert! is illustrative of the present state of Alzheimer's research: moving forward, optimistic, but still mostly a product of the pills and drugs old school of medicine. "Imagine the day when a routine visit to the family doctor includes a simple blood test to predict the risk for developing Alzheimer's disease (AD). If the test returns a worrisome result - too many sticky brain proteins that might begin to gum up memory and thought in 10 to 15 years - a person could be offered an aspirin-like pill to keep those proteins in check. ... we are at the threshold of developing therapies that we hope will eventually impact Alzheimer's disease. We are not slogging through a fog anymore. We can see the top of the hill for the first time ... I think Alzheimer's is going to be much easier to treat if you can prevent accumulation of [amyloid beta] in your brain, than if you try to treat it once plaques form. We know that statins don't work very well if a heart artery is 99 percent blocked, but do if they are taken earlier. The same thing would go for a drug designed to prevent Alzheimer's ... in the process, they are attempting to answer the question that has stumped the Alzheimer's research world: to what degree is [amyloid beta] responsible for the neurodegeneration seen in the disease ... That is the biggest secret in Alzheimer's disease research. We'd like to know what role it plays."
Another View of the Problem (July 24 2007)
Another view of the problem with the US regulation of research can be found in this review of futurist literature: "What really jumped out at me from both of these books is that much is possible, if we as a society (or the world) could just get past the 'monkeys with car keys' stage - we could achieve some truly great things. Maybe not absolute immortality, but maybe a much better and longer quality of life, for starters. Part of the stuff that needs to be discarded, IMHO, is dogma. That includes dogmatic religion, but also includes dogmatic ideologies that hold us back - this idea that man is meant to suffer is retarded and outright cruel, but it drives some of our laws. For instance, and this is the most glaring one (although I didn't corroborate this) is that a new drug cannot be brought into the U.S. market unless it's to treat a condition or disease. Read that again. So, if something is developed to extend life or extend your current capabilities, like vision or hearing, it will not be approved. It's the 21st century. How can this type of thinking still be with us?" It's quite true, and exactly why there are not dozens of companies in the US directly aiming at extending the healthy human life span. Those with the inclination are forced instead into disavowing any thought of treating the aging process. Their technological breakthroughs are relegated to patching up age-related diseases after the fact rather than reaching for rejuvenation and prevention of aging.
Is Living Longer Worth It? (July 24 2007)
Damn straight it is - but some paths to that goal are better than others. Here, Ronald Bailey reports at Reason Online from the ongoing Transvision 2007 conference: "The room was packed with 50 or so people interested in the issue of securing the 'longevity dividend.' ... The audience [ranged] from doctors, professors, and economists to people who had lived in alternative communities and even a few high school students. One might think that longer, healthier lives should be an easy sell, but, in fact, there are people who believe that dramatically extending human lives would be a bad idea. ... What is the longevity dividend? It's a way of rebranding the quest for extending human lives in a politically palatable way. ... [Aubrey de Grey] is pessimistic about the idea that the way the campaigners for the longevity dividend want to pursue it will result in reduced medical costs. ... American life expectancy has already increased by about seven years since 1960 and medical costs have obviously not gone down. Inherent in the idea of the longevity dividend is the notion of compressed mortality, that is, the period of decrepitude at the end of life will be shortened. De Grey argues that this not biologically plausible. ... Instead of pursuing the longevity dividend research agenda, De Grey wants to focus [on] rejuvenation interventions would repair the damage that aging produces in a person enabling them to live another 30 years. Then further research would develop better interventions that would repair the damage that occurs during that 30 year period and so forth. This series of anti-aging interventions would push death off indefinitely."
The Effects of Age On Stem Cells (July 23 2007)
From PLoS Biology, a close look at what happens to stem cells with advancing age. Getting down to the nuts and bolts both raises more questions than are answered, and sheds light on a range of areas, from regeneration through to cancer: "The effect of age on the regenerative capacity of adult stem cells, which should rejuvenate tissues throughout life, is poorly understood. Bone marrow stem cells, also known as hematopoietic stem cells (HSCs), continuously regenerate the cells that comprise the blood, including the immune system, which fails with age. Here, we show that older HSCs were less able to regenerate the blood system than young HSCs. Paradoxically, the HSC number increased concomitantly, leading to no major difference in overall blood production, even though the immune system did exhibit some defects. ... evidence supports the idea that loss of overall gene regulation (epigenetic regulation) is a major event during aging. Whereas much of aging research is concentrated on accumulation of mutations in DNA rather than on global regulatory mechanisms, we speculate that these epigenetic changes could drive many of the manifestations of age. This view also may explain the increased incidence of cancer with age."
Trends In Oxidative Aging Theories (July 23 2007)
This review paper caught my eye: "The early observations on the rate-of-living theory by Max Rubner and the report by Gershman that oxygen free radicals exist in vivo culminated in the seminal proposal in the 1950s by Denham Harman that reactive oxygen species are a cause of aging (free radical theory of aging). ... Because the free radical theory of aging is not the only theorem proposed to explain the mechanism(s) involved in aging at the molecular level, we also discuss how this theory is related to other areas of research in biogerontology, specifically, telomere/cell senescence, genomic instability, and the mitochondrial hypothesis of aging. ... It is now possible to give at least a partial answer to the question whether oxidative stress determines life span as Harman posed so long ago. Based on studies to date, we argue that a tentative case for oxidative stress as a life-span determinant can be made in Drosophila melanogaster. Studies in mice argue for a role of oxidative stress in age-related disease, especially cancer; however, with regard to aging per se, the data either do not support or remain inconclusive on whether oxidative stress determines life span."